Our group will investigate the mechanisms underlying the non-enzymatic glycosylation of hemoglobin and other proteins. We will determine the sites on the hemoglobin molecule that are modified both in vitro and in vivo. Careful measurements of the rates of glycosylation of hemoglobin under conditions simulating the interior of the red cell will determine whether measurement of Hb AIc is a reliable monitor of average blood sugar levels. The assessment of glycosylated hemoglobins in mammals as well as non-enzymatic glycosylation of other proteins may be greatly facilitated by the development of affinity chromatography for retrieval of these proteins. We plan detailed studies on proteins of the red cell membrane and of lens crystallins in normals and diabetics, and hope to ascertain whether non-enzymatic glycosylation affects function of these proteins.